innovaTV 207: Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03485209

Collaborator

Genmab (Industry), Merck Sharp & Dohme LLC (Industry)

532

Enrollment

Locations

Arms

78.2

Anticipated Duration (Months)

13.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will study tisotumab vedotin to find out whether it is an effective treatment for certain solid tumors and what side effects (unwanted effects) may occur. There are four parts to this study.

In Part A, the treatment will be given to participants every 3 weeks (3-week cycles).
In Part B, participants will receive tisotumab vedotin on Days 1, 8, and 15 every 4-week cycle.
In Part C, participants may receive tisotumab vedotin on Days 1 and 15 or Days 1, 8, and 15 on a 4-week cycle.
In Part D, participants will be given treatment on Day 1 of every 3-week cycle.

Participants in Part D will get tisotumab vedotin with either:

Pembrolizumab or,
Pembrolizumab and carboplatin, or
Pembrolizumab and cisplatin

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms Carcinoma, Non-Small-Cell Lung Exocrine Pancreatic Cancer Carcinoma, Squamous Cell of Head and Neck	Drug: tisotumab vedotin Drug: pembrolizumab Drug: carboplatin Drug: cisplatin	Phase 2

Detailed Description

The primary goal of this trial is to assess the activity, safety, and tolerability of tisotumab vedotin for the treatment of selected solid tumors. Patients will be treated with single agent tisotumab vedotin or tisotumab vedotin in combination with other agents. Patients who meet eligibility criteria will be enrolled into cohorts based on tumor type. Tumor types to be evaluated include colorectal cancer, squamous non-small cell lung cancer (NSCLC), exocrine pancreatic adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

532 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors

Actual Study Start Date :

Jun 25, 2018

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Tisotumab Vedotin - Q3W Schedule Tisotumab Vedotin every 3 weeks	Drug: tisotumab vedotin Given into the vein (IV; intravenously) Other Names: TIVDAK
Experimental: Part B: Tisotumab Vedotin - 3Q4W Schedule Tisotumab Vedotin on Days 1, 8, and 15 of 28-day cycle	Drug: tisotumab vedotin Given into the vein (IV; intravenously) Other Names: TIVDAK
Experimental: Part C: Tisotumab Vedotin - 3Q4W/2Q4W Schedule Tisotumab Vedotin on Days 1, 8, and 15 of a 28-day cycle and Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle	Drug: tisotumab vedotin Given into the vein (IV; intravenously) Other Names: TIVDAK
Experimental: Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule Tisotumab vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle.	Drug: tisotumab vedotin Given into the vein (IV; intravenously) Other Names: TIVDAK Drug: pembrolizumab 200mg given by IV Other Names: Keytruda Drug: carboplatin AUC 5mg/mL per minute given by IV Drug: cisplatin 100mg/m^2 given by IV

Outcome Measures

Primary Outcome Measures

Confirmed Objective Response Rate (ORR) [Up to approximately 3 years]
Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

Secondary Outcome Measures

Incidence of Adverse Events (AEs) [Up to approximately 3 years]
Type, severity, and relatedness of adverse events. An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Confirmed and Unconfirmed ORR [Up to approximately 3 years]
Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
Disease Control Rate (DCR) [Up to approximately 3 years]
Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator, or meet the SD criteria at least once after start of study treatment
Duration of Response (DOR) [Up to approximately 3 years]
Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first
Time to Response (TTR) [Up to approximately 3 years]
Time from the start of study treatment to the first documentation of objective response
Progression-free survival (PFS) [Up to approximately 3 years]
Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first
Overall Survival (OS) [Up to approximately 4 years]
Time from the start of study treatment to date of death due to any cause
Cmax [Through 30-37 days following the last dose; up to approximately 3 years]
Maximum observed plasma concentration
Ctrough [Through 30-37 days following the last dose; up to approximately 3 years]
Observed plasma concentration at the end of the dosing interval
Incidence of anti-therapeutic antibodies (ATAs) [Through 30-37 days following the last dose; up to approximately 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Parts A, B, and C
Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN patients who are not candidates for standard therapy.
All patients must have experienced disease progression on or after their most recent systemic therapy.
Colorectal cancer patients must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Patients should have received no more than 3 systemic regimens in the metastatic setting.
Patients with NSCLC must have predominant squamous histology. Patients must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible. Patients should have received no more than 3 lines of systemic therapy in the metastatic setting.
Patients eligible for a tyrosine kinase inhibitor should have received such therapy. These patients should have received no more than 4 lines of systemic therapy in the metastatic setting.
Patients with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. Patients must have received prior therapy with a gemcitabine-based or 5FU-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
Patients with SCCHN must have received prior therapy with a platinum-based regimen and/or a checkpoint inhibitor (CPI), if eligible, and must have experienced disease progression following such therapy. Participants should have received no more than 3 systemic lines of therapy in the recurrent or metastatic setting.
Part D
Participants with SCCHN must have received no previous systemic therapy in the recurrent or metastatic disease setting.
Participants with NSCLC must have histologically or cytologically documented squamous cell NSCLC and must have received no previous systemic therapy for metastatic disease or radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study treatment.
PD-L1 biomarker expression as determined by a PD-L1 IHC assay should be available
Able to provide fresh or archival tissue for biomarker analysis
Baseline measurable disease as measured by RECIST v1. 1.
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

Exclusion Criteria:

Participants with primary neuroendocrine or sarcomatoid histologies. For SCCHN, participants may not have a primary site of nasopharynx.
Active bleeding conditions
Ocular surface disease at the time of enrollment (Note: cataract is not considered active ocular surface disease for this protocol)
History of another malignancy within 3 years of the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
Uncontrolled tumor-related pain
Inflammatory lung disease. Participants with pulmonary disease are allowed if systemic steroids and long-term oxygen are not required
Peripheral neuropathy greater than or equal to Grade 2
Active brain metastasis
Part D Only: Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Sacramento	California	United States	95817
2	Stanford Cancer Center / Blood and Marrow Transplant Program	San Jose	California	United States	95124
3	Poudre Valley Health System (PVHS)	Fort Collins	Colorado	United States	80528
4	Yale Cancer Center	New Haven	Connecticut	United States	06520
5	Shands Cancer Center / University of Florida	Gainesville	Florida	United States	32610
6	University Cancer & Blood Center, LLC	Athens	Georgia	United States	30607
7	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia	United States	30322
8	Ingalls Cancer Care / Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
9	Community Health Network	Indianapolis	Indiana	United States	46250
10	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
11	Norton Cancer Institute	Louisville	Kentucky	United States	40202
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
13	HealthPartners Institute	Saint Louis Park	Minnesota	United States	55426
14	Weill Cornell Medicine	New York	New York	United States	10065
15	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina	United States	27599
16	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina	United States	27157
17	Oregon Health and Science University	Portland	Oregon	United States	97239-3098
18	Rhode Island Hospital	Providence	Rhode Island	United States	02903
19	Texas Oncology - Fort Worth	Dallas	Texas	United States	75246
20	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4095
21	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
22	Renovatio Clinical	The Woodlands	Texas	United States	77380
23	University of Virginia	Charlottesville	Virginia	United States	22903
24	University of Alberta / Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
25	Hospitalier Jean Minjoz	Besancon	Other	France	25030
26	Centre léon Bérard	LYON cedex 08	Other	France	69008
27	APHM Hôpital Nord	Marseille Cedex 20	Other	France	13915
28	Hopital Prive du Confluent	Nantes Cedex 2	Other	France	44277
29	Ruhr-Uni. Bochum, St. Josef-Hospital	Bochum	Other	Germany	44791
30	Universitätsklinikum Halle-Universitätsklinik und Poliklinik	Halle	Other	Germany	06120
31	Vincentius-Diakonissen-Kliniken gAG	Karlsruhe	Other	Germany	76137
32	Seconda Università degli Studi di Napoli, AOU	Napoli	Other	Italy	80131
33	Oncologia Medica, Ospedale Civile S. Maria delle Croci	Ravenna	Other	Italy	48121
34	PU Campus Bio-medico di Roma	Roma	Other	Italy	00128
35	Hospital Universitari Germans Trias i Pujol	Badalona	Other	Spain	08916
36	Hospital Quirónsalud Barcelona Instituto Oncologico Baselga	Barcelona	Other	Spain	08023
37	Hospital Universitario Vall d'Hebron	Barcelona	Other	Spain	08035
38	Hospital Universitario Ramon y Cajal	Madrid	Other	Spain	28034
39	HM Centro Integral Oncologico Clara Campal	Madrid	Other	Spain	28050
40	Guys and St Thomas Hospital	London	Other	United Kingdom	SE1 9RT